These studies are aimed at clarifying the pathogenesis of the Chediak-Higashi Syndrome, the cardinal feature of which is formation of giant (anomalous) lysosomes in many cell types. Using the mutant beige mouse, a homologue of the human disorder, unusual accumulations of age-related ceroid-like pigment are described in hepatocytes, renal proximal tubule cells, and splenic macrophages. These accumulations are seen as early as 1-2 weeks of age. They show cytochemically demonstrable acid phosphatase activity characteristic of lysosomes. The evidence suggests that such lipid accumulations may reflect an underlying defect in lipid metabolism in this disorder. Studies of alveolar macrophages of beige mice revealed a system of smooth endoplasmic reticulum that has acid phosphatase activity and appears to produce lysosomes. Tracer experiments with colloidal silver showed that, following nasal instillation, the marker was endocytosed and incorporated into this system. The findings suggest that endocytosed materials may be degraded in this system. Studies on the effects of carbachol, a cyclic guanosine-monophosphate elevating agent, on lysosome formation in the renal papilla of mice on potassium deficient diet, fail to support the view advanced by others that the Chediak-Higashi Syndrome involves a disturbance in microtubule stability or assembly. BIBLIOGRAPHIC REFERENCES: Oliver, C., Essner, E., Zimring, A. and Haimes, H. Age related accumulation of ceroid-like pigment in mice with Chediak-Higashi syndrome. Am. J. Pathol. 84:225-238, 1976. Swislocki, N.I., Tierney, J. and Essner, Edward S. Isolation and characterization of a liver plasma membrane fraction enriched in glucagon-sensitive adenylate cyclase. Arch. Biochem. Biophys. 174: 291-297, 1976.